Despite the detailed histological descriptions available in the literature, the mechanisms that control the processes of osteogenesis (endochondral and membranous), bone modelling, remodelling and repair are poorly understood. The investigation proposed will focus on the role of the cellular components in these processes. The primary objective is to determine which cell(s) in the adult mammal are capable of bone resorption, osteogenesis, or both. The investigation will attempt to answer the questions: Are there two main lines of precursor bone cells, each differentiating in only one direction, either into osteoclasts or into osteoblasts? If so, in which cell(s) does each function, bone resorption and formation, reside? If not, to what extent can the direction of differentiation of the progenitor cells be changed by changes in the milieu interieur and how does the ability for interconversion between osteoclasts and osteoblasts change with age? Using rabbits of varying ages, homogenous cell populations from a wide variety of tissue sources (i.e., undifferentiated blood cells, endothelial vascular and perivascular cells, monocytes, lymphocytes, macrophages, and endosteal and periosteal progenitor cells) will be isolated by both enzymatic and mechanical methods. Particular attention is being given to bone marrow cells isolated on bovine serum albumen continuous gradients. The final test of whether or not cell population is capable of bone resorption or osteogenesis will be, not morphological, but functional; i.e., whether or not it actually resorbs bone or forms it. These activities will be monitored in model systems using intra-peritoneal and muscular diffusion chambers which are impermeable to cells.